Journal of Thrombosis and Thrombolysis 18(2), 145–149, 2004.C© 2004 Kluwer Academic Publishers, Manufactured in The Netherlands.

Successful Lysis of Intra-Cardiac Thrombi withStreptokinase in Patients with Renal Failure; Two CaseReports and Review of the Literature

Walid Hassan MD, FACC, FACP, FCCP,1 FayezElShaer MD,1 Mohamed E.I.D. Fawzy MD, FRCP,FESC,1 Nathem Akhras PharmD,2 RashidAbdullah MD,1 Bahaa M. Fadel MD1

1Department of Cardiovascular Diseases,2 Department ofPharmacy, King Faisal Specialist Hospital and Research CenterRiyadh, Saudi Arabia

Abstract. In situ formation of thrombi within the car-diac cavities carries a substantial risk of morbidity andmortality due to the inherent danger of embolizationto vital organs. This typically occurs in patients withunderlying cardiac disorders associated with low flowstate favoring regional stagnation of blood and subse-quent clotting. Occasionally, extra-cardiac conditionssuch as renal failure predispose to the developmentof intra-cardiac thrombi in the presence or absence ofidentifiable cardiac abnormalities. Once identified, theappropriate treatment of such thrombi remains highlycontroversial. Here, we report on the successful andsafe use of streptokinase in two patients with end stagerenal disease with high risk left ventricular, right ven-tricular and right atrial thrombi.

Key Words. intra-cardiac, thrombi, renal failure,successful lysis, streptokinase

Introduction

The presence of intra-cardiac thrombi is a relativelycommon finding in a number of disorders associ-ated with global or segmental ventricular dysfunc-tion such as in dilated cardiomyopathy [1] and my-ocardial infarction as well as in conditions promotingblood stasis in the atria such as atrial fibrillation.Less common is the development of intra-cavitarythrombi in patients with hypercoagulable states inthe absence of an underling cardiac disorder. Suchconditions include Behcet’s disease, nephrotic syn-drome and renal failure among others.

The risk of systemic embolization from left-sidedintra-cavitary thrombi is highly variable, primar-ily depending on the characteristics of the underly-ing thrombi. For example, highly mobile, peduncu-lated and protruding thrombi, especially those witha narrow base of attachment, carry a higher risk ofembolization than those who are minimally mobile,sessile, not protruding and with a wide base of at-tachment. Reported rates of embolization from intra-cardiac thrombi vary widely according to above char-acteristics from 27% up to 60% in one series [2].

Definitive treatment of these intra-cardiacthrombi has yet to be established. Primary ther-apeutic options included surgical thrombectomy,anticoagulation and more recently, thrombolytictherapy. Few reports are available regarding theuse of anti-thrombin agents and glycoproteinIIb-IIIa inhibitors. No clear-cut recommendationsare currently available to guide the choice of therapy.

We have previously reported on the successfullysis of multiorgan thrombi in two patients withBehcet’s disease [3]. Hereby, we report the successfuluse of streptokinase in two patients with intra-cardiac thrombi in the setting of renal failure. Toour knowledge, probably this is the first report of thesafety and success of thrombolysis in patients withrenal failure and on hemodialysis.

Case Presentation

Case 1A 34-year old female with a history of coronaryartery disease and end-stage renal failure requiringhemodialysis underwent a routine echocardiogramas a work-up prior to kidney transplantation. Thisrevealed a large right atrial mass measuring 33 ×30 mm in the infero-superior and transverse diame-ters, respectively, attached to the right atrial wall ad-jacent to the mouth of the inferior vena cava (Fig. 1).No other abnormalities were noted and an echocar-diogram done 2 years earlier was unremarkable.A transesophageal echocardiogram showed that themass was partially surrounding a catheter that wasinserted via the right internal jugular vein two weeksearlier (Fig. 2). No clinical or echocardiographic stig-mata of endocarditis were noted. The patient was

Address for correspondence: Walid Hassan, MD, FACC, FACP,FCCP, Department of Cardiovascular Diseases (MBC 16), KingFaisal Specialist Hospital & Research Center, P.O. Box 3354,Riyadh 11211, Saudi Arabia. Fax: +966-1-442-7482; Tel: +966-1-442-7472; E-mail: hassanw@kfshrc.edu.sa

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146 Hassan et al.

Fig. 1. 2D echocardiogram 4 chambers view showing a largeright atrial mass.

Fig. 2. Transesophageal echocardiogram showing this large3.0 × 3.3 cm mass attached to the right atrial wall adjacent tothe mouth of the inferior vena cava.

initially started on intravenous heparin using ourweight-adjusted nomogram [4]. However, a repeatechocardiogram done 4 days later showed no signif-icant change in the size of the right atrial mass. In-travenous streptokinase was then started after in-formed consent as a 250,000 IU bolus followed bya continuous infusion at a rate of 100,000 IU/hour.Follow-up echocardiograms showed progressive de-crease in the size of the thrombus (Fig. 3) with acomplete resolution at day 7 of therapy (Figs. 4 and5). There were no complications and the patient wasmaintained on oral anticoagulation with no recur-rence.

Case 2A 29-year old female was known to have nephroticsyndrome secondary to membranoproliferativeglomerulonephritis, thrombocytopenic purpura and

Fig. 3. 2D echocardiogram showing decrease in thrombus sizeto 1.1 × 1.1 cm during streptokinase infusion.

Fig. 4. 2D echocardiogram at day 7 showed completeresolution of the right atrial thrombus.

Fig. 5. Tranesophageal echocardiogram at day 7 showingcomplete resolution of the right atrial thrombus.

Lysis of Intra-Cardiac Thrombi in Renal Failure 147

Fig. 6. CT scan showing right and left ventricular fillingdefects.

Fig. 7. 2D echocardiogram short axis view showing both rightand left ventricular large thrombi.

a transient ischemic attack 4 years earlier. Comput-erized Tomography (CT) Scan of the abdomen donefollowing an episode of acute renal failure revealedincidentally large masses (filling defect) in bothcardiac ventricles (Fig. 6). A surface echocardiogramshowed moderate left ventricular dysfunction, withmultiple clots in both ventricles (Fig. 7). Two of theseclots were large, highly mobile and pedunculatedthrombi measuring approximately 38 × 20 mm and25 × 14 mm, were attached to the left ventricularapex and the mid lateral wall, respectively (Figs. 8and 9). A large thrombus measuring 34 × 20 mmwas noted in the inflow portion of the right ventricle(Fig. 10). These thrombi were considered high risk forembolization. Accordingly, she was started initiallyon heparin infusion for 14 days with no significantreduction in the size of thrombi. Streptokinase wasthen given after informed consent at the same dose

Fig. 8. 2D echocardiogram long axis showing large apical leftventricular thrombus.

Fig. 9. 2D echocardiogram apical view showing the large,pedunculated, mobile thrombi with narrow base ofattachment to left ventricular lateral wall.

Fig. 10. 2D echocardiogram apical view showing the large,pedunculated, mobile thrombi with narrow base ofattachment to right ventricular inflow portion.

148 Hassan et al.

Fig. 11. 2D echocardiogram short axis view showing completeresolution of both right and left ventricular thrombi.

Fig. 12. 2D echocardiogram apical 4 chambers view showingcomplete resolution of both right and left ventricular thrombi.

mentioned above. A repeat echocardiogram 36 hourslater revealed complete resolution of all thrombi(Figs. 11 and 12), coupled with an improvement ofleft ventricular systolic function. There were no signsor symptoms of systemic or pulmonary emboliza-tion. The patient was maintained on chronic warfarintherapy, and a repeat echocardiogram six monthslater showed no recurrence.

Discussion

The development of intra-cavitary or mural cardiacthrombi has been well described in patients withunderlying cardiac disease. However, several pro-thrombotic entities, with or without an underly-ing cardiac disorder, may result in the formationof intra-cardiac thrombi. Renal failure, by virtue ofenhanced fibrin and platelets deposition, elevatedhomocysteine and endothelin levels, depressed ni-

tric oxide synthesis and vascular and endocardialcalcifications can result in a hypercoagulable state,especially in patients with underlying nephroticsyndrome.

The approach to the treatment of intra-cardiacthrombi is primarily focused on the prevention of sys-temic or pulmonary embolization and on the disso-lution of the thrombi themselves. Unfortunately, nopractice guidelines are currently available as to theproper management of such patients. In general, ses-sile and minimally mobile thrombi, especially thosecoating the endocardial surface are treated with longterm anticoagulation therapy aimed at preventingfurther growth of the thrombus. Treatment of highlymobile and pedunculated thrombi that carry a higherpotential for embolization remains highly controver-sial. High dose of intravenous heparin maintainingthe partial thromboplastin time (PTT) at 2–2.5 timesthe control value has been advocated as an effectivestrategy in dissolving the majority of left ventricularthrombi in one study [5]. However, this required amean duration of therapy of 14 days, and up to 22days in some patients, thus necessitating prolongedhospitalization and careful monitoring of PTT. Un-fortunately, this approach was not successful in oneof our patients.

Surgical thrombectomy is considered an effectivealternative therapy for high-risk thrombi. However,it requires a major surgery with the need for extra-corporeal circulation and carries a risk of perioper-ative morbidity and mortality, especially in patientswith underlying cardiac or systemic illnesses [6].

More recently, lysis of thrombi using intravenousthrombolytic agents has been advocated as more ef-fective than intravenous heparin and less invasivethan surgical thrombectomy. Before recombinant tis-sue plasminogen activator (rt-PA) became commer-cially available, the two primary thrombolytic agentsin use were streptokinase and urokinase. With thewithdrawal of urokinase from the US market, strep-tokinase became the most commonly used agent.

Intravenous thrombolytic therapy has proven ef-fective in the treatment of intr-acardiac thrombi.Kremer et al. [7] described 16 patients with recentmyocardial infarction and mural thrombi who weretreated with urokinase, achieving a complete lysisin 10 of 16 patients (62%) with newly formed clots,but only in 29% of those with older (more thanone month) clots. Two patients developed hematuriawhereas two others had no detectable change in thesize of the thrombus. Mathey et al. [8], likewise re-ported an approximate 66% rate of complete clot lysisusing urokinase and similar complication rate and alack of detectable embolization.

Keren et al. [9] reported lysis of a protruding mo-bile thrombus in four patients following myocardialinfarction using urokinase in one patient and strep-tokinase in three patients. In one of the three pa-tients, lysis of the thrombus was achieved without

Lysis of Intra-Cardiac Thrombi in Renal Failure 149

complications. In the latter two cases, however, sys-temic embolization occurred with transient diplopiain one and stroke followed by death in the other.Less experience is currently available with the useof newer thrombolytic agents such as rt-PA in suchpatients. A total of 7 thrombi in 4 patients were suc-cessfully lyzed using rt-PA without major complica-tions [10–13].

Whether heparin or one of the thrombolytic ther-apies provides a higher rate of thrombus dissolutionand/or safety in regard to embolization remains tobe determined. To the best of our knowledge, no ran-domized trials have been conducted comparing theefficacy and safety of heparin to that of thrombolyticagents. The heterogeneity of thrombi in regard totheir age, size, shape, location, mobility and otherdeterminants of lysis or embolization make such tri-als difficult to conduct. In the absence of any provenadvantage of one versus the other, our approach hasbeen to use a thrombolytic agent, in particular theless expensive and less rapidly acting streptokinaseat low maintenance dose, hoping to achieve a rela-tively slow clot lysis from the periphery to the bet-ter organized thrombus base and a lower risk ofembolization.

Conclusion

In summary, the identification of thrombi withinthe cardiac cavities poses a tremendous therapeu-tic challenge to the clinician. With the availabilityand widespread use of imaging studies, in particu-lar echocardiography, an increasing number of car-diac intra-cavitary thrombi are being recognized. Un-fortunately, the advances made in the recognitionand diagnosis of these thrombi has not been metwith equal advances in the decision making pro-cess regarding the most appropriate form of ther-apy. Our report confirms the efficacy and safetyof streptokinase in the treatment of intra-cardiacthrombi in patients with renal failure undergoinghemodialysis.

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